Pembrolizumab in Combination With Cisplatin and Intensity Modulated Radiotherapy (IMRT) in Head and Neck Cancer

NCT02777385 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 15-132
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to learn which therapy order (adding pembrolizumab during vs. after cisplatin and radiation) may be more effective in treating head and neck cancer, as well as learn the side effects of these combinations. Pembrolizumab is an immune therapy, a drug that stimulates the immune system to fight cancer, and is FDA approved in lung cancer and melanoma.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck; Locally Advanced; Squamous Cell Carcinoma; SCCHN; Untreated; High Risk; Intermediate Risk; Radiation Therapy; Cisplatin

Outcome Measures

Primary Outcomes (6)

• Progression-free Survival at ≤12 Months

  Probability of participants (expressed as a percentage) without disease progression at less than or equal to12 after start of treatment: Complete Response (CR) + Partial Response (PR)/total number of patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

  Up to 12 months

• Progression-free Survival at ≤ 36 Months

  Probability of participants (expressed as a percentage) without disease progression at less than or equal to 36 months after start of treatment: Complete Response (CR) + Partial Response (PR)/total number of patients assessed. Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

  Up to 36 months

• Progression-free Survival at ≤ 48 Months

  Probability of participants (expressed as a percentage) without disease progression time from treatment initiation to disease progression or death from any cause or last follow up. Per RECIST v1.1: Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

  Up to 48 months

• Acute Toxicity / DLT Rate

  The number of patients who experience unacceptable toxicity during protocol treatment as measured by the NCI CTCAE version 4.0

  Up to 6 months

• 1-year Locoregional Failure Rate

  Percent probability of participants for which time to locoregional failure (TTLRF) (calculated from treatment initiation to locoregional failure, or censored at other failure, death, or the last follow up; death is not an event) is less than 1 year. Locoregional failure is disease recurrence in either the location or regional location of the original disease, as opposed to a distant site.

  Up to 1 year

• 3-year Locoregional Failure Rate

  Percent probability of participants for which time to locoregional failure (TTLRF) (calculated from treatment initiation to locoregional failure, or censored at other failure, death, or the last follow up; death is not an event) is less than 3 years. Locoregional failure is disease recurrence in either the location or regional location of the original disease, as opposed to a distant site.

  Up to 3 years

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Up to 48 months

• Overall Survival (OS)

  Up to 48 months

• Overall Survival (OS) at ≤ 12 Months

  Up to12 months

• Overall Survival (OS) at ≤ 36 Months

  Up to 36 months

• Overall Survival (OS) at ≤ 48 Months

  Up to 48 months

Study Arms (2)

Arm 1

EXPERIMENTAL

Cisplatin, Radiation, and Pembrolizumab started 3 weeks after completion of cisplating and radiation.

Drug: Pembrolizumab; Drug: Cisplatin; Radiation: IMRT

Arm 2

EXPERIMENTAL

Cisplatin and Radiation and Pembrolizumab given 1 week prior to the start of cisp/radiation and given every 3 weeks

Drug: Pembrolizumab; Drug: Cisplatin; Radiation: IMRT

Interventions

Pembrolizumab DRUG

In both arms, the dose of pembrolizumab will be 200 mg (fixed dose) intravenous (IV) every 3 weeks for a total of 8 doses. In Arm 1, pembrolizumab will begin in week 10 of treatment, after cisplatin-IMRT is complete. In Arm 2, pembrolizumab will begin the week before cisplatin-IMRT.

Also known as: Keytruda

Arm 1; Arm 2

Cisplatin DRUG

Patients will receive cisplatin once weekly as an IV infusion over 60 minutes, for a total of 7 doses, at the same time as radiation.

Also known as: Platinol

Arm 1; Arm 2

IMRT RADIATION

IMRT will be delivered in 35 fractions (treatments) over 7 weeks (five treatments per non-holiday week) in one plan.

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• If a woman of childbearing potential, documentation of negative pregnancy
• Histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis. The primary site may be the oral cavity, oropharynx, larynx, or hypopharynx. Patients with squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes, are permitted to enroll.
• High risk or intermediate risk disease, defined below. Staging evaluation should be determined by imaging studies and complete head and neck exam in accordance with the American Joint committee on Cancer Staging Manual, 7th edition.
• o High risk patient must meet one of the following criteria:
• Surgically unresectable oral cavity. Patients who are technically resectable but refuse surgery due to morbidity (eg. total glossectomy) are also eligible. Medically inoperable patients are not eligible.
• Larynx: T4 any N; T2-3 and ≥ N2a
• Hypopharynx: T1-2N1-3 or T3-4N0-3
• Oropharynx: p16(-) AND T3-4 or ≥ N2a
• Unknown primary: p16(-) AND ≥ N2a
• o Intermediate risk patients must meet one of the following criteria:
• Oropharynx: p16(+) AND one of the following
• T3 or ≥ N2a AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form, Appendix A)
• T4 or N3 disease irrespective of tobacco exposure
• Unknown primary: p16(+) AND one of the following

You may not qualify if:

• Nasopharyngeal primary site
• Current participation in or previous participation in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent.
• Distant metastatic disease including CNS or leptomeningeal metastases is not allowed.
• History of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Received prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• History of second malignancy within 2 years prior to Study Day 1 (except for excised and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial bladder cancer, or T1a or T1b prostate cancer comprising \< 5% of resected tissue with normal prostate specific antigen (PSA) since resection).
• Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Received a live vaccine within 30 days prior to the first dose of trial treatment.
• Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Significant pulmonary disease, including pulmonary hypertension, interstitial lung disease, or active, non-infectious pneumonitis.
• History or current evidence of any other medical or psychiatric condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Peripheral neuropathy ≥ Grade 2

Sponsors & Collaborators

• Dan Zandberg: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (2)

• Zandberg DP, Vujanovic L, Clump DA, Isett BP, Wang H, Sica G, Bao R, Li H, Ohr J, Skinner HD, Seethala RR, Chiosea SI, Ferris RL, Bauman JE. Randomized Phase II Study of Concurrent Versus Sequential Pembrolizumab in Combination With Chemoradiation in Locally Advanced Head and Neck Cancer. J Clin Oncol. 2025 Aug 10;43(23):2572-2582. doi: 10.1200/JCO-24-01580. Epub 2025 May 27.

  PMID: 40424564 DERIVED

• Ferris RL, Moskovitz J, Kunning S, Ruffin AT, Reeder C, Ohr J, Gooding WE, Kim S, Karlovits BJ, Vignali DAA, Duvvuri U, Johnson JT, Petro D, Heron DE, Clump DA, Bruno TC, Bauman JE. Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer. Clin Cancer Res. 2022 Apr 1;28(7):1335-1344. doi: 10.1158/1078-0432.CCR-21-0426.

  PMID: 35091445 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

pembrolizumab; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Dan Zandberg, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 28, 2016
• First Posted: May 19, 2016
• Study Start: May 31, 2016
• Primary Completion: April 24, 2023
• Study Completion: May 4, 2023
• Last Updated: August 1, 2024
• Results First Posted: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)